MYT1L encodes a neuron-specific transcription factor. MYT1L was first reported in relation to autosomal dominant syndromic complex neurodevelopmental disorder in 2007 (de Ligt et al., PMID: 23033978). The disorder is characterized by developmental delay with significant speech and language delay, mild to severe intellectual disability, behavioral disorders including autism, hyperphagia, obesity or overweight, and dysmorphic features. Other variable features include hypotonia, seizures, and brain MRI abnormalities. Individuals with 2p25.3 deletions encompassing MYT1L exhibit an overlapping phenotype, indicating that MYT1L is the causal gene (PMID: 2523284).
At least ten unique MYT1L sequence variants have been reported. Ten variants (nonsense, frameshift, splice site, and missense) that have been reported in ten probands in four publications (PMIDs: 23033978, 25232846, 28859103, 30055078) are included in this curation. All variants occurred de novo. The mechanism of pathogenicity is loss of function.
This gene-disease relationship is also supported by animal models and in vitro functional studies. Myt1l plays a key role in neuronal differentiation by repressing expression of non-neuronal genes during neuron differentiation (PMID: 28379941) and promotes differentiation of oligodendrocyte precursor cells (PMID: 29397565).
In summary, there is definitive evidence supporting the relationship between MYT1L and autosomal dominant syndromic complex neurodevelopmental disorder. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on August 18, 2020 (SOP Version 7). As of October 2025, this record underwent administrative updates to update scoring to be consistent with SOP Version 11. No new evidence has been added.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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